sirolimus + calcineurin inhibitors

A **combination immunosuppressive therapy** utilizing sirolimus (an mTOR inhibitor) plus one or more calcineurin inhibitors (such as tacrolimus or cyclosporine) predominantly in solid organ transplantation (e.g., kidney, heart, simultaneous heart-kidney). **Sirolimus** inhibits mTOR after binding FKBP-12, arresting immune cell proliferation and reducing cytokine signaling, while **calcineurin inhibitors** block T-cell activation by inhibiting calcineurin-mediated NFAT dephosphorylation and downstream cytokine gene transcription. This combination can allow for dose minimization and reduced nephrotoxicity compared to standard calcineurin inhibitor regimens, and may preserve renal function and long-term graft survival when properly dosed[1][3][4][6].